Is PDE6C p.Ala264Val (c.791C>T) pathogenic?

PDE6C p.Ala264Val (c.791C>T) is classified Uncertain significance in PDE6C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-14). AlphaMissense: likely benign (0.2902); Ultra-rare (popmax 0.0282%, afr); Associated with Inborn genetic diseases.

What condition is associated with PDE6C p.Ala264Val (c.791C>T)?

PDE6C p.Ala264Val (c.791C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PDE6C p.Ala264Val (c.791C>T) in the general population?

PDE6C p.Ala264Val (c.791C>T) is ultra-rare (popmax 0.0282%, afr) (gnomAD).

What do computational predictors say about PDE6C p.Ala264Val (c.791C>T)?

AlphaMissense predicts likely benign (score 0.2902) — an in-silico prediction, not a clinical call.

PDE6C p.Ala264Val

c.791C>T · rs143673530 · VCV1002667

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2902 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2902	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -4.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.51	GERP 1.3, phastCons 0.064
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	17.29	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0282% African / African-American · 21/74,514 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.00478% 77/1,612,284 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0282%	3,548
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	0.00424%	23,585
South Asian	0.0011%	90,938

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PDE6C
Protein: p.Ala264Val
Coding: c.791C>T
MANE Select: NM_006204
dbSNP: rs143673530
Type: single nucleotide variant
Location: chr10:93621999 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.53 · 7 PDB
Residue 264: the gaf 2 domain; an α-helix

Full PDE6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE6C p.Ala264= Conflicting classifications of pathogenicity ★ same residue
PDE6C p.Ala264Glu Uncertain significance ★ ⚠ same residue
PDE6C p.Ala462Val Uncertain significance ★★ ⚠ same condition
PDE6C p.Ala668Thr Uncertain significance ★★ ⚠ same condition
PDE6C p.Arg527Gln Uncertain significance ★★ ⚠ same condition
PDE6C p.Arg95Cys Uncertain significance ★★ ⚠ same condition
PDE6C p.Asn16Lys Uncertain significance ★★ ⚠ same condition
PDE6C p.Asn611Ser Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pde6c-p-ala264val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown